Phylogenomic analyses identifies dog-human sharing of genetically closely related Escherichia coli, including carbapenemase OXA-244 producing and colistin resistant strains

Introduction: In Nigeria, a large proportion of dogs are free roaming or semi-restricted; a practice that brings them in close contact with potentially virulent and antibiotic resistant bacteria in the community. We investigated the role of dogs as community reservoir for dissemination of Escherichia coli resistant to "high priority critically important antimicrobials" in Makurdi, North central Nigeria.

Methods: We subjected a total of 137 isolates to whole genome sequencing and uploaded the reads unto the EnteroBase server which facilitates genome assembly, core and whole genome based phylogenomic analyses. Genome assemblies were queried for resistance determinants using AMRFinder while phenotypic expression of resistance was assessed based on the antibiotic minimum inhibitory concentration (MIC).

Results: Hierarchical clustering analyses of core genome multilocus sequence types (cgMLST) revealed a genetically diverse population of 34 clonal complexes (CC) predominated by CC10. We identified the blaOXA244 cabarpenemase gene in two isolates and the plasmid mediated colistin resistance gene variants: mcr-1.22, mcr-10.1, with the former located on an IncX4 plasmid. Multiple strains harbored extended spectrum β-lactamases (ESBL) genes predominantly blaCTX-M-15 (n=50) and blaCTX-M-55 (n=6). Isolates expressed cefotaxime and colistin resistance and a meropenem MIC of 0.125 µg/ml, respectively. Comparative phylogenomic analyses revealed close genetic relationship at HC5 (pairwise genetic distance of ≤ 5 cgMLST allelic difference) between canine isolates and human strains recovered from the same geographic location in Nigeria, suggestive of potential human-dog exchange of strains. Additional closely related genomes were detected among sequence data publicly available from EnteroBase.

Conclusion: Our findings show that dogs in developing countries are an important reservoir for potential community dissemination of colistin resistant, ESBL and carbapenemase producing E. coli, reechoing concerns for zoonotic and bidirectional spread.